tetano
Editor, Senior Moderator
Transbound Emerg Dis
. 2020 Aug 13.
doi: 10.1111/tbed.13792. Online ahead of print.
Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV
Qiong Wang[SUP] 1 [/SUP], Ye Qiu[SUP] 1 [/SUP], Jin-Yan Li[SUP] 1 [/SUP], Ce-Heng Liao[SUP] 1 [/SUP], Zhi-Jian Zhou[SUP] 1 [/SUP], Xing-Yi Ge[SUP] 1 [/SUP]
Affiliations
Abstract
Coronavirus (CoV) pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, severe acute respiratory syndrome CoV (SARS-CoV) caused SARS pandemic in 2003 and SARS-CoV-2 caused the ongoing COVID-19 pandemic. Both viruses are most likely originated from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Especially, SARS-CoV-2 tended not to use murine or non-mammal ACE2s. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. Nevertheless, the actually susceptibility of these animals to the coronaviruses should be further verified by in-vivo studies. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20[SUP]th[/SUP] and 42[SUP]nd[/SUP] amino acid residues that might determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies enhance the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.
Keywords: SARS-CoV; SARS-CoV-2; angiotensin converting enzyme 2 (ACE2); coronavirus; host range; interspecies transmission; receptor utilization.
. 2020 Aug 13.
doi: 10.1111/tbed.13792. Online ahead of print.
Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV
Qiong Wang[SUP] 1 [/SUP], Ye Qiu[SUP] 1 [/SUP], Jin-Yan Li[SUP] 1 [/SUP], Ce-Heng Liao[SUP] 1 [/SUP], Zhi-Jian Zhou[SUP] 1 [/SUP], Xing-Yi Ge[SUP] 1 [/SUP]
Affiliations
- PMID: 32794346
- DOI: 10.1111/tbed.13792
Abstract
Coronavirus (CoV) pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, severe acute respiratory syndrome CoV (SARS-CoV) caused SARS pandemic in 2003 and SARS-CoV-2 caused the ongoing COVID-19 pandemic. Both viruses are most likely originated from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Especially, SARS-CoV-2 tended not to use murine or non-mammal ACE2s. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. Nevertheless, the actually susceptibility of these animals to the coronaviruses should be further verified by in-vivo studies. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20[SUP]th[/SUP] and 42[SUP]nd[/SUP] amino acid residues that might determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies enhance the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.
Keywords: SARS-CoV; SARS-CoV-2; angiotensin converting enzyme 2 (ACE2); coronavirus; host range; interspecies transmission; receptor utilization.